Spatial exploration induces a persistent reversal of long-term potentiation in rat hippocampus
Abstract
Experience-dependent long-lasting increases in excitatory synaptic transmission in the hippocampus are believed to underlie certain types of memory. Whereas stimulation of hippocampal pathways in freely moving rats can readily elicit a long-term potentiation (LTP) of transmission that may last for weeks, previous studies have failed to detect persistent increases in synaptic efficacy after hippocampus-mediated learning. As changes in synaptic efficacy are contingent on the history of plasticity at the synapses, we have examined the effect of experience-dependent hippocampal activation on transmission after the induction of LTP. We show that exploration of a new, non-stressful environment rapidly induces a complete and persistent reversal of the expression of high-frequency stimulation-induced early-phase LTP in the CA1 area of the hippocampus, without affecting baseline transmission in a control pathway. LTP expression is not affected by exploration of familiar environments. We found that spatial exploration affected LTP within a defined time window because neither the induction of LTP nor the maintenance of long-established LTP was blocked. The discovery of a novelty-induced reversal of LTP expression provides strong evidence that extensive long-lasting decreases in synaptic efficacy may act in tandem with enhancements at selected synapses to allow the detection and storage of new information by the hippocampus.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Although the initiation of phase 2 is theorized to involve a calcium-triggered reduction in the sensitivity of NMDA receptors, its maintenance over hours to days may involve depotentiating mechanisms.
“Although the initiation of phase 2 is theorized to involve a calcium-triggered reduction in the sensitivity of NMDA receptors, its maintenance over hours to days may involve depotentiating mechanisms as well (Xu et al. [284]; Rowan et al. [285]; Zhuo et al. [286]; Ghetti and Heinemann [287]; Adamec et al. [288]; Lin et al. [289]; Manahan-Vaughan and Kulla [290]; Kemp and Manahan-Vaughan [117]; G”
From The Temporal Dynamics Model of Emotional Memory Processing: A Synthesis on the Neurobiological Basis of Stress-Induced Amnesia, Flashbulb and Traumatic Memories, and the Yerkes-Dodson Law (2007) · cites this paper as Xu et al. [284]
Cites
Two-stage model of memory trace formation: A role for “noisy” brain states
Buzsáki, G. (1989) · Neuroscience · doi:10.1016/0306-4522(89)90423-5 · Cited by 1,709 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Stress and the brain: from adaptation to disease
de Kloet, E. R., Joëls, M., & Holsboer, F. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1683 · Cited by 4,621 · see citing works
The Psychology and Neuroscience of Forgetting
Wixted, J. T. (2004) · Annual Review of Psychology · doi:10.1146/annurev.psych.55.090902.141555 · Cited by 999 · see citing works
Long-term depression in the CNS
Collingridge, G. L., Peineau, S., Howland, J. G., & Wang, Y. T. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2867 · Cited by 926 · see citing works
Diamond, D. M., Campbell, A. M., Park, C. R., Halonen, J., & Zoladz, P. R. (2007) · Neural Plasticity · doi:10.1155/2007/60803 · Cited by 762 · see citing works
“…reduction in the sensitivity of NMDA receptors, its maintenance over hours to days may involve de-potentiating mechanisms as well (Xu et al. [284]; Rowan et al. [285]; Zhuo et al. [286]; Ghetti and Heinemann [287]; Adamec et al. [288]; Lin et al. [289]; Manahan-Vaughan and Kulla [290]; Kemp…”
BackgroundBekinschtein, P., Cammarota, M., Igaz, L. M., Bevilaqua, L. R. M., Izquierdo, I., & Medina, J. H. (2007) · Neuron · doi:10.1016/j.neuron.2006.11.025 · Cited by 633 · see citing works
Dopamine-dependent facilitation of LTP induction in hippocampal CA1 by exposure to spatial novelty
Li, S., Cullen, W. K., Anwyl, R., & Rowan, M. J. (2003) · Nature Neuroscience · doi:10.1038/nn1049 · Cited by 568 · see citing works
Self-citationMemristor-based neural networks
Thomas, A. (2013) · Journal of Physics D: Applied Physics · doi:10.1088/0022-3727/46/9/093001 · Cited by 471 · see citing works
Chronic stress: Implications for neuronal morphology, function and neurogenesis
Joëls, M., Karst, H., Krugers, H. J., & Lucassen, P. J. (2007) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2007.04.001 · Cited by 381 · see citing works
Memory retention – the synaptic stability versus plasticity dilemma
Abraham, W. C., & Robins, A. (2005) · Trends in Neurosciences · doi:10.1016/j.tins.2004.12.003 · Cited by 353 · see citing works
Moncada, D., & Viola, H. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.1083-07.2007 · Cited by 370 · see citing works
PKMζ maintains memories by regulating GluR2-dependent AMPA receptor trafficking
Migues, P. V., Hardt, O., Wu, D. C., Gamache, K., Sacktor, T. C., Wang, Y. T., & Nader, K. (2010) · Nature Neuroscience · doi:10.1038/nn.2531 · Cited by 283 · see citing works
Plastic modifications induced by object recognition memory processing
Clarke, J. R., Cammarota, M., Gruart, A., Izquierdo, I., & Delgado-García, J. M. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0915059107 · Cited by 273 · see citing works
Hippocampal long-term depression mediates spatial reversal learning in the Morris water maze
Dong, Z., Bai, Y., Wu, X., Li, H., Gong, B., Howland, J. G., Huang, Y., He, W., Li, T., & Wang, Y. T. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.06.027 · Cited by 219 · see citing works
LTP consolidation: Substrates, explanatory power, and functional significance
Lynch, G., Rex, C. S., & Gall, C. M. (2007) · Neuropharmacology · doi:10.1016/j.neuropharm.2006.07.027 · Cited by 214 · see citing works
The role of metaplasticity mechanisms in regulating memory destabilization and reconsolidation
Finnie, P. S. B., & Nader, K. (2012) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2012.03.008 · Cited by 189 · see citing works
Prince, T.-M., Wimmer, M., Choi, J., Havekes, R., Aton, S., & Abel, T. (2014) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2013.11.021 · Cited by 142 · see citing works
On Common Ground: Jost's (1897) Law of Forgetting and Ribot's (1881) Law of Retrograde Amnesia.
Wixted, J. T. (2004) · Psychological Review · doi:10.1037/0033-295x.111.4.864 · Cited by 140 · see citing works
Synaptic basis for whisker deprivation-induced synaptic depression in rat somatosensory cortex
Bender, K. J., Allen, C. B., Bender, V. A., & Feldman, D. E. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.0175-06.2006 · Cited by 126 · see citing works
Lynch, G., Kramár, E. A., Babayan, A. H., Rumbaugh, G., & Gall, C. M. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.07.006 · Cited by 97 · see citing works
Diamond, D. M., Park, C. R., & Woodson, J. C. (2004) · Hippocampus · doi:10.1002/hipo.10186 · Cited by 95 · see citing works
Maroun, M. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.05169.x · Cited by 82 · see citing works
Zhang, Y., Mao, R.-R., Chen, Z.-F., Tian, M., Tong, D.-L., Gao, Z.-R., Huang, M., Li, X., Xu, X., Zhou, W.-H., et al. (2014) · Molecular Brain · doi:10.1186/1756-6606-7-11 · Cited by 69 · see citing works
Self-citationSegatto, M., Leboffe, L., Trapani, L., & Pallottini, V. (2014) · Current Medicinal Chemistry · doi:10.2174/0929867321666140303142902 · Cited by 65 · see citing works
- Authors
- Xu, L., Anwyl, R., & Rowan, M. J.
- Affiliations
- Trinity College Dublin (IE)
- Venue
- Nature
- Published
- 1998-08
- Volume
- 394
- Issue
- 6696
- Pages
- 891-894
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1519786933
- Cited by
- 260
- References
- 1
- Citations by year
- 2025: 6 · 2024: 2 · 2023: 3 · 2021: 5 · 2020: 2 · 2019: 11 · 2018: 4 · 2017: 11 · 2016: 5 · 2015: 7 · 2014: 12 · 2013: 8 · 2012: 15
- FWCI
- 5.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Wellcome Trust
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- long-term potentiation, hippocampus, CA1, spatial exploration, novelty, synaptic plasticity, synaptic efficacy, memory, hippocampus-dependent learning, excitatory synaptic transmission
- MeSH terms
- Animals, Exploratory Behavior, Hippocampus, Learning, Male, Time Factors, Rats, Wistar, Long-Term Potentiation, Excitatory Postsynaptic Potentials, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
